Isaacson J S
Department of Physiology and Biophysics, University of Washington, Seattle 98195, USA.
J Neurophysiol. 1998 Sep;80(3):1571-6. doi: 10.1152/jn.1998.80.3.1571.
Large nerve terminals (calyces of Held) in the medial nucleus of the trapezoid body (MNTB) offer a unique opportunity to explore the modulation of presynaptic channels at a mammalian central synapse. In this study I examined gamma-aminobutyric acid-B (GABAB)-mediated presynaptic inhibition at the calyx of Held in slices of the rat auditory brain stem. The selective GABAB agonist baclofen caused a potent inhibition of synaptic transmission and presynaptic Ca2+ current. The inhibition of presynaptic Ca2+ channels was associated with a slowing of the activation kinetics of the underlying current, and the inhibition was relieved by strong depolarization. The inhibition of both synaptic transmission and presynaptic Ca2+ current was abolished by N-ethylmaleimide, a sulfhydryl alkylating agent that uncouples the G(o)/Gi class of G proteins from receptors. Baclofen does not activate a potassium conductance in the presynaptic terminal. Taken together, these results suggest that GABAB receptors inhibit synaptic transmission via G protein-mediated modulation of presynaptic Ca2+ channels at this large central synapse. Furthermore, these findings demonstrate that basic mechanisms of G protein-mediated inhibition of Ca2+ channels, proposed from recordings of neuron cell bodies, are well conserved at nerve endings in the mammalian brain.
梯形体内侧核（MNTB）中的大型神经末梢（ Held壶腹）为探索哺乳动物中枢突触处突触前通道的调节提供了独特的机会。在本研究中，我检测了大鼠听觉脑干切片中 Held壶腹处γ-氨基丁酸B（GABAB）介导的突触前抑制。选择性GABAB激动剂巴氯芬对突触传递和突触前Ca2+电流产生了强效抑制作用。突触前Ca2+通道的抑制与基础电流激活动力学的减慢有关，且强去极化可解除这种抑制。N-乙基马来酰亚胺（一种使G(o)/Gi类G蛋白与受体解偶联的巯基烷基化剂）可消除对突触传递和突触前Ca2+电流的抑制。巴氯芬不会激活突触前终末的钾电导。综上所述，这些结果表明，在这个大型中枢突触处，GABAB受体通过G蛋白介导的突触前Ca2+通道调节来抑制突触传递。此外，这些发现表明，从神经元细胞体记录中提出的G蛋白介导的Ca2+通道抑制的基本机制在哺乳动物脑的神经末梢中保存得很好。
